Trial Outcomes & Findings for Study to Evaluate Safety and Efficacy of Benralizumab in Subjects With Hypereosinophilic Syndrome (NCT NCT02130882)

Last Updated: 2022-02-08

Results Overview

50% reduction in peripheral blood eosinophilia on stable HES background therapy at 12 weeks post-initiation of study drug

Recruitment status

UNKNOWN

Study phase

PHASE2/PHASE3

Target enrollment

20 participants

Primary outcome timeframe

3 months

Results posted on

2022-02-08

Participant Flow

Participant milestones

Participant milestones
Measure	Drug Benralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. benralizumab: An afucosylated humanized antibody to IL-5 receptor alpha	Placebo Placebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. Placebo: A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline
Overall Study STARTED	10	10
Overall Study COMPLETED	10	9
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Drug Benralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. benralizumab: An afucosylated humanized antibody to IL-5 receptor alpha	Placebo Placebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. Placebo: A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Study to Evaluate Safety and Efficacy of Benralizumab in Subjects With Hypereosinophilic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Drug n=10 Participants Benralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. benralizumab: An afucosylated humanized antibody to IL-5 receptor alpha	Placebo n=10 Participants Placebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. Placebo: A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline	Total n=20 Participants Total of all reporting groups
Age, Continuous	46 years n=5 Participants	44 years n=7 Participants	45 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Clinical Subtype Myeloid variant	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Clinical Subtype Lymphoid variant	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Clinical Subtype Single organ overlap	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Clinical Subtype Idiopathic	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Eosinophil count	2331 cells per microliter n=5 Participants	2535 cells per microliter n=7 Participants	2431 cells per microliter n=5 Participants

PRIMARY outcome

Timeframe: 3 months

50% reduction in peripheral blood eosinophilia on stable HES background therapy at 12 weeks post-initiation of study drug

Outcome measures

Outcome measures
Measure	Drug n=10 Participants Benralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. benralizumab: An afucosylated humanized antibody to IL-5 receptor alpha	Placebo n=10 Participants Placebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. Placebo: A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline
Number of Participants With 50% Reduction in Peripheral Blood Eosinophilia	9 Participants	3 Participants

SECONDARY outcome

Timeframe: 3 months

Percent reduction in peripheral blood eosinophilia at 12 weeks post-treatment

Outcome measures

Outcome measures
Measure	Drug n=10 Participants Benralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. benralizumab: An afucosylated humanized antibody to IL-5 receptor alpha	Placebo n=10 Participants Placebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. Placebo: A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline
Percent Reduction in Eosinophil Count	100 Percent reduction in eosinophil count Interval 49.0 to 100.0	14 Percent reduction in eosinophil count Interval -15.0 to 89.0

Adverse Events

Drug

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Drug n=10 participants at risk Benralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. benralizumab: An afucosylated humanized antibody to IL-5 receptor alpha	Placebo n=10 participants at risk Placebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. Placebo: A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline
Vascular disorders hypotension	0.00% 0/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • Number of events 1 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.

Other adverse events

Additional Information

Dr. Amy Klion

National Institute of Allergy and Infectious Diseases, NIH

Phone: 301-435-8903

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Drug n=10 participants at risk Benralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. benralizumab: An afucosylated humanized antibody to IL-5 receptor alpha	Placebo n=10 participants at risk Placebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered. Placebo: A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline
Blood and lymphatic system disorders Lymphocytopenia	60.0% 6/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Nervous system disorders Headache	70.0% 7/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Investigations Elevated serum lactic dehydrogenase	50.0% 5/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Blood and lymphatic system disorders Anemia	70.0% 7/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
General disorders Fatigue	50.0% 5/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
General disorders Chills	50.0% 5/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Gastrointestinal disorders Nausea	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Gastrointestinal disorders Abdominal cramps	30.0% 3/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	0.00% 0/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Renal and urinary disorders Elevated creatinine	30.0% 3/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	0.00% 0/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Musculoskeletal and connective tissue disorders Pain in hip	30.0% 3/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Infections and infestations Upper respiratory infection	30.0% 3/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
General disorders Fever	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	0.00% 0/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Gastrointestinal disorders Decreased appetite	30.0% 3/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	0.00% 0/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Investigations Hyponatremia	30.0% 3/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	0.00% 0/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Blood and lymphatic system disorders Neutrophilia	20.0% 2/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Investigations Hypophosphatemia	20.0% 2/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	40.0% 4/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
General disorders Malaise	20.0% 2/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Skin and subcutaneous tissue disorders Pruritic rash	20.0% 2/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	30.0% 3/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Renal and urinary disorders Elevated urinary white blood cell count	20.0% 2/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	10.0% 1/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.
Investigations Elevated C-reactive protein	20.0% 2/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.	0.00% 0/10 • 12 weeks At each contact with the subject, information regarding adverse events was elicited by appropriate questioning and examinations.